Giardia, the most prevalent intestinal parasitic pathogen in humans and animals, is transmitted via contaminated food and water and is endemic in much of the world, resulting in estimates of 1 billion cases annually. In developed regions of the world, Giardia is primarily transmitted by a direct fecal-oral route, in freshwater supplies, and by occasional outbreaks from municipal water supplies, with estimates of from 500,000 to 2 million cases in the U.S. annually.
Infection results from ingestion of Giardia cysts that develop into trophozoites in response to the pH and enzyme environmental stresses present within the stomach. Within the small intestine, the trophozoites must attach to the intestinal wall to prevent expulsion by peristalsis and to initiate infection. This attachment is primarily mediated by a novel mechanical force, in contrast to the more typical receptor-ligand mechanism used by many pathogens. Despite research by several groups over the past four decades, remarkably little is understood about the processes by which Giardia parasites attach.
Infection can start with as few as 10 cysts, and an infected individual can release millions of cysts. Most infections are either asymptomatic or self-limiting, but a subset of individuals become chronically infected with weight loss and fail to thrive as a consequence. Symptoms include malabsorptive diarrhea, cramps, and flatulence. Both symptomatic and asymptomatic individuals transmit the parasite.
No vaccine is currently available for use, and disease control relies solely on a limited set of chemotherapeutic agents. In the U.S., clinically recognized cases are often treated with metronidazole, although this agent is not indicated for the treatment of giardiasis. Certain other nitroimidazoles, nitrofurans, and benzimidazoles can be used as secondary treatments.
While metronidazole is often effective, recurrence rates as high as 90% have been reported. Adverse reactions, including nausea, diarrhea, and/or metallic taste in the mouth, are also commonly reported. Some less common, but equally unpleasant, side effects are also associated with metronidazole administration. Most compounds, including metronidazole, require a relatively long period of administration (5-10 days), resulting in a low compliance rate. While shorter treatments are possible with certain agents, the incidence and severity of side effects typically then increases sharply. Furthermore, resistance to each of these drugs (up to 20% for metronidazole), and multi-drug resistance has been documented, and different parasite genotypes appear to have different drug sensitivities.
With limited treatment options, the unwanted side effects of currently used chemotherapeutic agents, parasite drug resistance, the number of incidences, and the high potential for transmission, giardiasis is a public health concern here and abroad. AIDS patients and pregnant women present particularly challenging treatment situations. Accordingly, there is a need to expand the limited repertoire of treatments for Giardia exposure and infection.